Fish Epigenetics: Molecular Mechanisms, Environmental Adaptation, and Emerging Computational Approaches

Abstract

Epigenetic regulation has transformed our understanding of how fish adapt to changing environments by modulating gene expression without altering the underlying DNA sequence. This review explores the “dark mastery” of fish epigenetics by providing mechanistic insights into the principal epigenetic processes, including DNA methylation, histone modifications, chromatin remodeling, and non-coding RNAs, that govern development, immunity, stress responses, and disease susceptibility. These regulatory mechanisms enable fish to respond dynamically to environmental stressors such as temperature fluctuations, salinity shifts, hypoxia, pollutants, ultraviolet radiation, and nutritional changes, thereby influencing physiological resilience, reproductive performance, and survival. Recent advances in next-generation sequencing and multi-omics technologies have substantially expanded our understanding of the fish epigenome, while bioinformatics has become indispensable for integrating and interpreting complex genomic, transcriptomic, and epigenomic datasets. Furthermore, artificial intelligence (AI) and machine learning (ML) are emerging as powerful approaches for biomarker discovery, predictive modeling of disease susceptibility, environmental risk assessment, and precision aquaculture. The integration of epigenetics with bioinformatics and AI provides unprecedented opportunities to decipher complex regulatory networks, identify adaptive epigenetic signatures, and develop data-driven strategies for improving fish health and aquaculture sustainability. Despite these advances, important challenges remain, including limited species-specific epigenomic resources, difficulties in multi-omics integration, model interpretability, and the need for standardized analytical frameworks. This review highlights current knowledge, emerging computational approaches, and future perspectives for translating epigenetic discoveries into sustainable aquaculture practices and aquatic ecosystem conservation under accelerating environmental change.

1. Introduction

Fish occupy highly dynamic aquatic environments in which temperature [1], salinity [2], dissolved oxygen [3], pH [4], nutritional availability [5], pollutants [6], pathogens [7], and other ecological variables can fluctuate over relatively short temporal and spatial scales [8]. The capacity of fish to cope with such environmental heterogeneity depends not only on genetic variation but also on regulatory mechanisms that modulate gene activity without changing the underlying DNA sequence [9]. Epigenetic regulation has therefore emerged as an important molecular interface between environmental conditions and phenotype, providing a mechanistic framework for understanding how environmental information can be translated into changes in development, physiology, metabolism, reproduction, immunity, stress tolerance, and adaptation [10]. This perspective is particularly relevant to fishes because of their diverse life histories, high developmental plasticity, aquatic exposure pathways, and importance in both natural ecosystems and aquaculture [11]. Recent studies increasingly indicate that environmentally responsive epigenetic mechanisms may contribute to phenotypic plasticity and, under specific circumstances, influence responses across generations.

The fish epigenome is regulated through interconnected molecular mechanisms rather than through a single epigenetic pathway. DNA methylation, particularly at CpG sites, can influence transcriptional activity and is extensively studied in relation to development, sex determination, reproduction, environmental stress, and phenotypic variation. Histone post-translational modifications regulate chromatin accessibility and transcriptional states, whereas ATP-dependent chromatin-remodeling processes and higher-order chromatin organization provide additional levels of transcriptional control [12]. Non-coding RNAs, including microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), further regulate gene expression through post-transcriptional and chromatin-associated mechanisms. Importantly, these regulatory layers interact. Consequently, an observed change in DNA methylation, histone modification, or ncRNA expression should not necessarily be interpreted as an isolated molecular event; rather, its biological significance must be considered within the broader regulatory and cellular context [13]. Although DNA methylation remains the most extensively characterized epigenetic mark in fish, the increasing availability of multi-omic technologies is beginning to reveal more complex relationships among epigenetic layers and transcriptional phenotypes [13].

Environmental conditions represent a major source of epigenetic variation in fish. Thermal regimes can alter DNA methylation and other regulatory processes associated with development, sex differentiation, metabolism, reproduction, and stress responses [14]. Similarly, salinity, hypoxia, pH, nutritional conditions, and anthropogenic contaminants have been associated with changes in epigenetic profiles and the expression of genes involved in stress responses, metabolism, immunity, and reproduction [15]. Recent research in environmental epigenetics suggests that such changes may reflect phenotypic plasticity or acclimation rather than adaptive evolution itself. Distinguishing environmentally induced plastic responses from genetically based adaptation therefore remains a fundamental challenge. This distinction is especially important when interpreting claims of epigenetic inheritance, because persistence of an epigenetic mark across generations does not by itself demonstrate that the mark is causally responsible for an adaptive phenotype [16]. Establishing such relationships requires carefully controlled experiments, appropriate temporal and generational designs, and functional validation.

The relevance of epigenetic regulation extends beyond ecological physiology to aquaculture [2]. Production environments impose a combination of environmental, nutritional, developmental, and management-related conditions that can influence epigenetic states [17]. Epigenetic mechanisms have consequently been investigated in relation to growth, development, sex determination, reproduction, stress tolerance, immune responses, disease resistance, and other commercially important traits [18]. Epigenetic information may eventually complement conventional genetic selection by helping identify biomarkers associated with desirable phenotypes or by informing environmental and nutritional interventions [19]. However, translation into routine aquaculture practice remains limited. Epigenetic signatures can be strongly dependent on tissue type, developmental stage, environmental history, genetic background, and experimental conditions, while correlations between epigenetic marks and phenotypes do not necessarily establish causality [20]. The stability, reproducibility, and predictive value of candidate epigenetic biomarkers therefore require validation across independent populations and production environments [21].

Technological advances have transformed the scale at which these questions can be investigated. Genome-wide methylation profiling, reduced-representation sequencing, whole-genome bisulfite sequencing, long-read sequencing, chromatin profiling, transcriptomics, and other high-throughput approaches now permit increasingly comprehensive characterization of fish epigenomes [22]. These datasets, however, are highly dimensional and context-dependent, creating substantial analytical challenges. Bioinformatics provides the computational foundation for quality control, methylation analysis, differential epigenomic analysis, functional annotation, multi-omic integration, and comparative interpretation [23]. More recently, machine-learning and predictive modeling approaches have been applied to fish epigenetic datasets for applications including age and sex prediction and the identification of environmentally responsive molecular biomarkers [24]. Recent evidence demonstrates that such approaches can generate useful predictive models, but the published literature remains relatively limited compared with the broader field of fish epigenetics. Thus, the current evidence does not yet justify treating artificial intelligence as a mature or broadly established tool for fish epigenetic research. Instead, computational approaches should be evaluated according to the biological data used, prediction objective, model design, validation strategy, interpretability, and performance in independent datasets [25].

Despite rapid growth in fish epigenetics, the field remains fragmented across molecular, ecological, aquaculture, and computational disciplines [26]. Several unresolved issues limit the development of a unified understanding of how epigenetic regulation contributes to fish phenotypes. First, research remains disproportionately focused on individual epigenetic mechanisms, particularly DNA methylation, whereas the functional interactions among DNA methylation, histone modifications, chromatin organization, and non-coding RNAs remain comparatively less resolved. A mechanistic understanding requires moving beyond cataloging epigenetic differences toward determining how these regulatory layers interact with transcriptional and physiological processes.

Second, substantial context dependence complicates comparisons among studies. Epigenetic profiles can differ according to species, tissue, developmental stage, sex, environmental history, exposure intensity, and duration. Consequently, the same environmental factor may produce different opposing epigenetic responses in different biological contexts. This heterogeneity makes it difficult to identify conserved epigenetic signatures of stress and resilience [16].

Third, an important conceptual gap persists between epigenetic response, phenotypic plasticity, acclimation, and adaptation. Although environmentally induced epigenetic changes are increasingly reported, relatively few studies establish whether such changes directly contribute to fitness-related phenotypes or persist sufficiently to influence subsequent generations. Evidence for transgenerational inheritance therefore requires particularly cautious interpretation and rigorous experimental validation [27].

Fourth, the application of epigenetics to aquaculture remains largely at the experimental and proof-of-concept stage. Candidate biomarkers associated with growth, sex, stress tolerance, or disease resistance require validation across genetic backgrounds and realistic production environments before they can support breeding or management decisions. Integration of epigenetic information with conventional genetic selection also remains an emerging area requiring further empirical evidence [28].

Finally, computational analysis represents both an opportunity and a methodological challenge. The increasing volume and complexity of epigenomic data creates a strong rationale for machine-learning and other predictive approaches, yet published applications in fish remain limited and are concentrated in selected areas such as DNA methylation-based prediction [29]. Important methodological questions concerning sample size, feature selection, overfitting, cross-validation, external validation, model interpretability, and biological reproducibility remain insufficiently addressed [30]. Moreover, proposed applications involving the integration of epigenetic, environmental, microbiome, and disease data should be distinguished from applications that have already been experimentally demonstrated [19].

These gaps highlight the need for an integrated assessment of fish epigenetics that connects molecular mechanisms, environmental regulation, biological outcomes, aquaculture relevance, and computational analysis rather than treating these areas as independent topics. Accordingly, this review critically evaluates the current evidence, emphasizes areas where causal or predictive evidence remains limited, and identifies methodological priorities for advancing the field.

Despite substantial advances in fish epigenetics, several important knowledge gaps remain unresolved. Current research has predominantly focused on individual epigenetic mechanisms, particularly DNA methylation, while the functional interactions among DNA methylation, histone modifications, chromatin remodeling, and non-coding RNAs remain comparatively less understood [31]. Interpretation is further complicated by strong context dependence, as epigenetic profiles can vary with species, tissue type, developmental stage, sex, genetic background, environmental history, and exposure intensity [32]. Consequently, epigenetic alterations identified under particular experimental conditions cannot necessarily be generalized across fish environmental contexts [33]. A further conceptual challenge is distinguishing environmentally induced epigenetic responses from phenotypic plasticity, acclimation, and genuine adaptation [34]. Although numerous studies have reported environmentally associated epigenetic changes, relatively few have established whether these alterations are causally linked to ecologically or commercially relevant phenotypes or persist sufficiently to influence subsequent generations [35]. In aquaculture, epigenetic biomarkers have shown promise for understanding growth, reproduction, stress tolerance, sex determination, and disease resistance, but their translation into breeding and management programs remains constrained by limited cross-population validation, tissue specificity, environmental variability, and uncertainty regarding causality and reproducibility [36]. At the same time, the rapid expansion of high-throughput epigenomic datasets has created opportunities for bioinformatics, machine-learning, and predictive modeling; however, experimentally validated computational applications in fish remain relatively limited, with most existing work concentrated on DNA methylation-based prediction. Important methodological challenges, including limited sample sizes, feature selection, overfitting, model interpretability, independent validation, and biological reproducibility, therefore require greater attention [37]. These limitations highlight the need for an integrated perspective that connects molecular epigenetic mechanisms with environmental regulation, phenotypic outcomes, aquaculture applications, and computational analysis [38]. Accordingly, this review critically synthesizes current evidence to distinguish established mechanisms from emerging hypotheses, evaluate the strength and limitations of available evidence, and identify priorities for experimental validation and practical application in fish biology, aquaculture, and environmental management.

2. Review Methodology

This review was developed through a structured literature-based synthesis of published research on fish epigenetics [39]. Relevant scientific literature was identified through searches of major academic literature databases and search engines using combinations of keywords related to the main themes of the review [40]. The literature search focused on studies addressing fish epigenetics, DNA methylation, histone modifications, chromatin regulation, non-coding RNAs, environmental stress and adaptation, aquaculture, and emerging computational and machine-learning approaches [41].

The literature was selected based on its relevance to the objectives and thematic scope of the review [42]. Particular attention was given to primary research articles and recent studies that provided experimental or computational evidence concerning epigenetic regulation in fish [43]. Relevant review articles were also consulted to provide broader conceptual background and to identify important primary studies. Additional relevant publications were identified by examining the reference lists of key articles [44].

The selected literature was organized thematically rather than quantitatively pooled. The major themes included (i) molecular mechanisms of fish epigenetic regulation, (ii) epigenetic responses to environmental factors and their potential role in adaptation, (iii) applications of epigenetics in aquaculture and fish health, and (iv) emerging computational and machine-learning approaches in fish epigenetic research. Within these themes, findings from different studies were compared to identify common patterns, contrasting observations, methodological limitations, and important knowledge gaps [45].

For the computational component, particular attention was given to studies in which epigenetic data were directly analyzed using machine-learning or predictive approaches [46]. Where available, information concerning the type of epigenetic data, prediction target, computational model, validation approach, and reported performance was considered [47]. This approach was used to distinguish experimentally demonstrated applications from proposed or prospective applications of artificial intelligence [48].

The literature was not treated as a simple collection of individual findings. Instead, studies were critically interpreted in relation to species differences, developmental stage, tissue type, environmental conditions, experimental design, epigenetic mechanism, and biological outcome [49]. Evidence that was inconsistent, limited, or insufficiently validated was identified accordingly. Studies unrelated to fish epigenetics or that did not contribute directly to the major themes of the review were not included in the final synthesis.

The study is intended as a narrative and critical review rather than a formal systematic review or meta-analysis; no formal PRISMA workflow or quantitative meta-analysis was performed. The purpose of the literature search was to provide a focused and integrative assessment of the current state of knowledge, emphasizing mechanistic understanding, environmental and aquaculture relevance, emerging computational applications, current limitations, and directions for future research.

3. Ecological Impact on Fish Health

One of the fundamental ecological impacts of epigenetics on fish health lies in their adaptive capacity to environmental variability [50]. Fish species inhabit diverse aquatic environments ranging from freshwater to deep-sea habitats, each presenting unique challenges such as temperature fluctuations, salinity changes, and varying levels of pollutants [51]. Epigenetic mechanisms, particularly DNA methylation and histone modifications, allow fish to adjust their gene expression profiles rapidly in response to these environmental cues [52]. For instance, studies have shown that epigenetic modification can alter thermal tolerance in fish species like European sea bass, influencing their distribution patterns in rivers and oceans as temperatures change due to climate variability or anthropogenic factors [53]. Moreover, epigenetics also plays a crucial role in regulating immune responses and disease resistance in fish populations [54]. Environmental stressors, pathogens, and pollutants can induce epigenetic changes that affect genes involved in immune function. It is essential for managing disease outbreaks in both wild fish populations and aquaculture settings. For example, epigenetic research has identified markers associated with immune response pathways in species like trout and carp, providing insights into enhancing disease resilience and sustainable aquaculture practice [55]. Furthermore, epigenetic modification impacts behavioral traits critical for survival and reproductive success in fish. Changes in gene expression patterns influenced by epigenetic mechanisms can affect mating behaviors, migration patterns, and parental care strategies. For instance, epigenetic regulation plays a role in smoltification, a critical developmental process preparing juvenile salmon for migration from freshwater to marine environments [56,57]. Disruption in these epigenetic processes due to environmental stressors can impair reproductive fitness and population dynamics, affecting species conservation efforts and overall ecosystem health [58]. In the context of ecosystem structure and function, fish health influenced by epigenetic factors contributes significantly to maintaining biodiversity and ecosystem services [59]. Healthy fish populations play a vital role in trophic interactions, regulating prey populations, and contributing to nutrient cycling through their feeding and excretion activities [60]. Epigenetic studies help elucidate how changes in fish populations due to disease outbreaks, pollution, and climate change can cascade through ecosystems, influencing community composition and ecosystem resilience [61]. An integrated approach for ecosystem-based fisheries management is needed: insights from ecosystem-level management strategy evaluation. The application of epigenetics in conservation and management practices is increasingly recognized for its potential to inform decision-making and enhance ecological resilience [62]. Monitoring epigenetic markers can provide valuable indicators of population health and adaptive potential in response to environmental changes [63]. This information is critical for designing effective conservation strategies, such as habitat restoration initiatives and species reintroduction programs, to preserve biodiversity and restore ecosystem functions [64].

4. Economic Impact on Fish Health

Fish health is pivotal for maintaining ecological balance and sustaining global economic activities, notably fisheries and aquaculture [65]. Epigenetics, a field within molecular biology, offers profound insight into molecular mechanisms underlying fish health and disease resilience [66]. It is essential to uncover the environmental factors that influence gene expression and phenotypic traits in fish populations through the study of epigenetic markers. It not only enhances the understanding of fish health dynamics but also informs strategies for sustainable fisheries management, disease prevention in aquaculture, and conservation efforts aimed at preserving wild fish populations and their habitats [67]. According to the World Bank, diseases impose an estimated annual economic burden of $6 billion USD on the global aquaculture industry. Global economic losses due to fish diseases in a recent year, the estimated figure for 2022 was around $10 billion USD. Reducing these costs is a major challenge, and often, there is no straightforward solution. Moreover, aquaculture is an important sector for global food security and economic development. Epigenetic research in aquaculture focuses on enhancing disease resistance and improving growth rates in farmed species such as salmon, trout, and shrimp [54]. In commercial fisheries, the sustainability and productivity of fish stocks are directly impacted by environmental changes and fishing pressures. Epigenetic tools offer a way to assess the adaptive potential of fish populations to these stressors [68]. They help to understand the epigenetic mechanisms related to reproductive success, migration patterns, and population dynamics. Fisheries managers can make informed decisions about stock enhancement programs and habitat conservation. For example, epigenetic studies have highlighted that changes in gene expression patterns influenced by environmental factors can affect the timing of spawning migration in salmonids, influencing their availability for commercial harvest [69]. The application of epigenetics in fisheries and aquaculture is also linked to broader social benefits, including food security, employment opportunities, and economic stability in coastal communities [70]. Sustainable management practices informed by epigenetic research can support the long-term viability of fisheries and aquaculture industries, ensuring reliable food production and economic growth while minimizing environmental impacts. For example, aquaculture producers can reduce susceptibility to disease outbreaks and improve overall farm activity through selective breeding based on epigenetic markers [71]. Thereby, it may enhance profitability and market competitiveness.

5. Artificial Intelligence and Machine Learning in Fish Epigenetics and Disease Prediction

Artificial intelligence and machine learning have emerged as powerful tools for analyzing complex biological datasets generated from modern sequencing technologies [72]. In fish health research, these approaches are particularly valuable for integrating large-scale multi-omics datasets, including genomic, transcriptomic, and epigenomic information [73]. Machine learning algorithms can identify hidden relationships between environmental stressors and epigenetic modifications that may influence disease susceptibility, immune responses, and physiological adaptation in fish populations (Figure 1) [74]. Several computational approaches have been applied in aquatic research, including supervised learning methods such as random forest, support vector machines, and neural networks, as well as unsupervised learning techniques like clustering and dimensionality reduction [75]. These methods allow researchers to identify epigenetic biomarkers associated with environmental stress, disease resistance, and immune system regulation [76]. For example, machine learning models can analyze genome-wide DNA methylation patterns to predict fish responses to temperature fluctuations, pollution exposure, and pathogen infections [77]. In aquaculture systems, AI-based predictive models can support early detection of disease outbreaks by integrating environmental monitoring data, microbial community dynamics, and epigenetic markers

Table 1. Machine-learning applications for prediction using fish epigenetic and epigenomic biomarkers.

Species	Epigenetic Data	ML/Predictive Approach	Prediction/Application	Key Result	Reference
Dicentrarchus labrax (European sea bass)	DNA methylation of seven sex-related genes; targeted bisulfite sequencing	Machine-learning classification	Prediction of phenotypic sex from methylation markers	Selected CpGs, particularly in cyp19a1a, were used to predict sex with approximately 90% accuracy. The study demonstrated that environmentally responsive epigenetic marks can provide predictive information on phenotype.	[79]
Dicentrarchus labrax (European sea bass)	DNA methylation at 48 CpGs in four genes	Penalized regression/epigenetic-clock modeling	Chronological-age prediction	A DNA-methylation-based epigenetic clock was developed to predict fish age, demonstrating the feasibility of ML-based methylation biomarkers for fisheries applications.	[80]
Danio rerio (zebrafish)	DNA methylation of promoter regions of genes involved in sex differentiation and stress responses	Flexible discriminant analysis (FDA) with cross-validation	Prediction of sex and previous developmental thermal exposure	Methylation of cyp19a1a predicted sex with approximately 88% accuracy. Methylation of amh and foxl2a was also able to classify fish according to previous exposure to elevated temperature, with reported accuracies of approximately 71% and 78%, respectively.	[81]
Dicentrarchus labrax (European sea bass) larvae	Genome-wide methylation detected from environmental DNA using nanopore sequencing	Model-selection/predictive epigenetic-clock framework	Non-invasive age prediction	DNA methylation from eDNA was used to estimate larval age. The model achieved a cross-validated median absolute error of approximately 2.6 days, demonstrating the potential of epigenetic prediction using environmental samples.	[82]
Fish model used for aquaculture breeding	~500,000 CpG loci from sperm; heritable epigenetic biomarkers	Feature selection and multiple ML algorithms	Prediction of broodstock performance	Three heritable CpG markers were associated with offspring biomass, female growth, and resistance to temperature-induced masculinization. ML models were used to identify broodstock based on epigenetic biomarkers and were validated in independent trials.	[83]
Gadus morhua (Atlantic cod)	47,000+ CpGs from fin tissue; bis-RAD-seq	Machine-learning epigenetic-clock model	Chronological-age prediction for fisheries management	A model based on 73 CpGs predicted age with 97.5% accuracy and approximately 2.8-month precision and generalized to unseen samples and geographically distinct fish.	[84]

[78].

Such predictive frameworks can improve farm management practices, reduce economic losses, and minimize the need for antibiotics and chemical treatments [85]. Additionally, machine learning can assist in identifying candidate genes and epigenetic signatures associated with disease resistance, facilitating selective breeding programs for more resilient fish stocks [74]. Furthermore, AI-driven approaches are increasingly being used to analyze microbiome-host interactions in aquatic ecosystems [86]. By combining environmental microbiology data with epigenetic profiles, researchers can better understand how microbial communities influence fish immunity and stress responses [87]. These integrative computational frameworks will play an important role in advancing precision aquaculture and ecosystem-based fisheries management [88]. Despite its promising potential, the application of machine learning in fish epigenetics research still faces several challenges, including data standardization, limited availability of annotated datasets, and the need for interdisciplinary expertise [89]. Future research should focus on developing robust computational pipelines that integrate multi-omics datasets with advanced machine learning techniques to improve disease prediction, environmental monitoring, and sustainable aquaculture practices [90].

6. Major Fish Health Issues in Aquaculture

In aquaculture, a significant challenge revolves around maintaining optimal fish health amidst various stressors, with epigenetics emerging as a critical area of study to understand and address these issues. One of the major health concerns in aquaculture is disease susceptibility, exacerbated by intensive farming conditions where fish are often subjected to high stocking densities and environmental stressors [91]. Pathogens such as bacteria, viruses, fungi, and parasites thrive under these conditions, leading to disease outbreaks that can decimate fish populations and impact production sustainability [92]. Epigenetic mechanisms, including DNA methylation, histone modifications, and microRNA regulation, influence the expression of genes involved in immune responses and disease resistance in fish [93]. For instance, environmental stressors like poor water quality or temperature fluctuations can trigger epigenetic changes that alter immune system function, making fish more susceptible to infections [94]. Furthermore, epigenetics contributes to improving overall fish health by optimizing growth rates, reproductive success, and stress tolerance [95]. It is possible to mitigate risks, reduce antibiotic use, and foster sustainable aquaculture practices that ensure the health and resilience of farmed fish populations by unraveling the intricacies of epigenetic regulation in aquaculture species [96]. In aquaculture, epigenetics contributes to enhancing disease resistance and improving productivity. High stocking densities and environmental stressors in aquaculture settings can lead to disease outbreaks [97]. Epigenetic studies have identified markers associated with immune function and stress responses in farmed fish, guiding breeding programs to develop resilient strains that thrive in challenging environments [97]. This application of epigenetics supports sustainable aquaculture practices by reducing reliance on antibiotics and chemical treatments, thereby minimizing environmental impacts and promoting health [98].

7. Invasive Species Bringing New Diseases

Invasive species introducing new diseases pose a significant threat to fish health in both natural ecosystems and aquaculture settings, with epigenetics offering valuable insights into understanding and mitigating these challenges [99]. Epigenetic modifications can influence susceptibility to pathogens introduced by invasive species, impacting disease dynamics and ecological interactions within aquatic ecosystems [100]. Monitoring epigenetic responses in native fish populations can inform invasive species management strategies, helping mitigate disease risks and protect biodiversity [50]. Native fish populations may not have acquired defenses against new illnesses and parasites that non-native species may introduce into their new environments [101]. This scenario often leads to disease outbreaks that can devastate local biodiversity and impact aquaculture operations worldwide. Moreover, invasive species may introduce new pathogens, and native fish may undergo epigenetic modifications that influence their immune responses, stress tolerance, and disease susceptibility [102]. For example, changes in DNA methylation patterns or histone modifications can regulate the expression of genes involved in immune function and inflammatory responses [103]. Developing effective management strategies against diseases introduced by invasive species is important. Epigenetic changes influence disease resistance in native fish populations, and researchers can identify potential biomarkers for early detection of pathogen exposure and predict susceptibility to specific diseases [104]. This knowledge can inform proactive measures such as enhancing biosecurity protocols, implementing quarantine procedures, and developing targeted vaccination programs to protect vulnerable fish populations in aquaculture facilities [105]. Furthermore, epigenetics offers insights into the transgenerational effects of invasive species-induced diseases [106]. Changes in epigenetic marks induced by pathogen exposure may be inherited by offspring, influencing their susceptibility to similar diseases in subsequent generations [107]. This phenomenon underscores the importance of considering long-term impacts and adaptive responses in managing fish health amidst invasive species threats [108]. The practical applications of epigenetics in mitigating the impacts of invasive species on fish health include enhancing genetic diversity within aquaculture populations, promoting selective breeding for disease-resistance traits, and optimizing environmental management strategies [109]. Epigenetic data can be used for aquaculture practice, and various types of stakeholders can enhance the resilience of native fish species to emerging diseases introduced by invasive species while minimizing ecological disruptions and conserving biodiversity in vulnerable ecosystems [110].

8. Climate Change

Climate change poses significant challenges to aquatic ecosystems, affecting fish populations in numerous ways, including through the alteration of epigenetic processes [111]. In the context of fish, these epigenetic modifications can occur in response to various environmental stressors, including increased incidence of viruses and bacterial infections exacerbated by climate change [112]. Climate change affects aquatic ecosystems through multiple mechanisms, including rising water temperatures, ocean acidification, altered precipitation patterns, and changes in habitat availability [113]. These environmental changes can disrupt the delicate balance of marine and freshwater ecosystems, leading to shifts in species distributions, changes in predator-prey dynamics, and altered reproductive behaviors among fish populations [114]. For example, most fish are ectotherms, which means that temperature has a significant impact on their physiology. Temperature influences their metabolic rate, as well as their energy balance and behavior, which includes locomotor and eating behavior [115]. It can also influence the distribution of pathogens and parasites that affect fish health. Heating water can promote the growth and spread of disease-causing organisms, such as bacteria and viruses, in aquatic environments, increasing the likelihood of infections among fish populations [116]. In the context of infections, exposure to pathogens can induce changes in the epigenetic profiles of fish. For instance, infection with viruses or bacteria can lead to alterations in DNA methylation patterns in immune-related genes, affecting the fish’s ability to mount an effective immune response [117]. These epigenetic changes can have lasting effects on immune system function, potentially increasing susceptibility to subsequent infections or affecting the ability of fish to adapt to changing environmental conditions [97]. Climate change significantly contributes to the proliferation and spread of viruses and bacterial infections in fish through various mechanisms. Changes in precipitation patterns and ocean currents alter habitat dynamics, exposing fish to infectious agents in new geographic areas previously unaffected. Additionally, rising atmospheric carbon dioxide levels lead to ocean acidification, stressing fish and weakening their immune systems, which can disrupt microbial communities and potentially foster the growth of harmful pathogens [118]. Moreover, the increase in frequency and intensity of extreme weather events associated with climate change, such as storms and floods, further disrupts aquatic ecosystems, heightening stress levels and susceptibility to infections among fish populations [119]. Climate change is a significant driver of environmental change with profound implications for fish populations and aquatic ecosystems. Increased incidence of viruses and bacterial infections in fish, exacerbated by climate change, can lead to epigenetic modifications that affect immune responses and overall health [120]. Addressing these challenges requires integrated approaches that consider the complex interactions between environmental factors, fish biology, and epigenetic mechanisms [121]. Continued research and conservation efforts are essential to safeguarding fish populations and maintaining the resilience of aquatic ecosystems in a changing climate.

9. Value of Studying Fish Health Regarding Epigenetics

Studying fish health through the lens of epigenetics offers profound insights into the interplay between environmental factors and genetic expression, providing critical implications for both aquatic ecosystems and human welfare. Fish are highly sensitive to environmental changes due to their direct exposure to aquatic habitats, making them excellent indicators of ecosystem health [122]. Epigenetic mechanisms, including DNA methylation, histone modification, and non-coding RNA regulation, allow fish to adapt their gene expression patterns in response to environmental cues. For instance, changes in water temperature, pH levels, or exposure to pollutants can trigger epigenetic modifications that alter gene expression related to immune response, metabolism, and reproductive health in fish populations [123]. Moreover, the value of studying fish health through epigenetics extends beyond ecological conservation to human health and food security [124]. Researchers can establish techniques to reduce the harmful effects of environmental stresses on fish health by understanding these mechanisms, ensuring stable food sources and economic stability for fishery-dependent populations [125]. Furthermore, epigenetics in fish health provides insights into broader evolutionary processes and the potential for adaptive responses in changing environments. This knowledge can inform conservation efforts by identifying populations or species at higher risk of extinction due to environmental changes and guiding targeted conservation interventions [126]. Additionally, epigenetic studies in fish health contribute to advancing biomedical research and pharmaceutical development [127]. Fish models are increasingly used in biomedical research due to genetic and physiological similarities with humans. Understanding epigenetic mechanisms in fish can provide insights into human diseases influenced by environmental factors, such as cancer, metabolic disorders, and immune dysfunction, thereby facilitating the development of targeted therapies and preventive measures [128]. The value of studying fish health through the lens of epigenetics lies in its interdisciplinary implications for environmental science, human health, and conservation biology [129]. Researchers can improve ecosystem management techniques, ensure sustainable fisheries, and contribute to worldwide efforts to promote environmental sustainability and human well-being by understanding how epigenetic pathways impact fish responses to environmental stressors [130].

10. Development of Genomics and Epigenetics

The development of genomics and epigenetics has profoundly reshaped our understanding of biological systems and their implications across diverse fields [131]. Genomics, propelled by advancements in next-generation sequencing (NGS) technologies, has facilitated comprehensive studies of an organism’s entire DNA sequence, paving the way for breakthroughs in genetic diversity, evolutionary relationships, and precision medicine [132]. Next-generation sequencing (NGS) technologies and long-read Oxford Nanopore sequencing have revolutionized the study of DNA methylation, offering complementary strengths and capabilities in epigenetic research [133]. NGS platforms, such as Illumina sequencing, are renowned for their high-throughput capabilities, precise base calling, and cost-effectiveness, making them ideal for genome-wide methylation profiling [134]. NGS can accurately detect methylated cytosines (5mC) across the genome by utilizing bisulfite conversion methods, thereby providing insights into epigenetic modifications associated with gene regulation, development, and disease [76]. In contrast, long-read sequencing technologies, notably Oxford Nanopore sequencing, offer unique advantages by generating exceptionally long reads that can span repetitive regions and complex genomic structures [135]. This capability is particularly advantageous in studying DNA methylation, as it allows for the direct detection of modified bases without the need for bisulfite conversion [136]. Oxford Nanopore sequencing also enables the detection of other epigenetic modifications, such as DNA modifications by DNA base editors and RNA modifications, further broadening its utility in epigenomics research [137]. The combination of NGS and long-read sequencing approaches enriches the study of DNA methylation by providing comprehensive and complementary perspectives [138]. NGS delivers high-resolution, genome-wide methylation maps with precise quantification, while long-read sequencing offers insights into the context and distribution of methylation patterns within complex genomic regions [139]. Together, these technologies accelerate the discovery of epigenetic mechanisms underlying phenotypic variation, disease susceptibility, and cellular differentiation, paving the way for transformative advancements in biomedical research and personalized medicine [140]. Bioinformatics tools have been crucial in managing the vast amounts of genomic data generated, enabling genome assembly, annotation, and comparative analyses that underpin key discoveries in genetics [141]. Concurrently, epigenetics has emerged as a pivotal area elucidating how external and environmental factors influence gene expression without altering the DNA sequence itself [142]. The discovery and characterization of epigenetic mechanisms, including DNA methylation, histone modifications, and non-coding RNA regulation, have revealed dynamic layers of gene regulation that contribute to development, disease susceptibility, environmental responses, and adaptation in fish [143]. Advanced sequencing techniques like ChIP-seq and bisulfite sequencing have empowered researchers to map epigenetic modifications genome-wide, unraveling complex regulatory networks and their roles in health and disease (Figure 2) [144]. The integration of genomics and epigenetics has fostered a systems biology approach that integrates multiple omics disciplines to provide holistic insights into biological functions and disease mechanisms [145]. These fields are essential to environmental research because they provide insight into species adaptation, biodiversity protection, ecosystem resilience, and biomedical implications [146]. Moreover, their applications extend to agriculture and biotechnology, where they drive innovations in crop improvement, disease resistance, and sustainable agricultural practices [147]. Genomics and epigenetics continue advancing our understanding of life’s intricacies, offering transformative opportunities to address global health, agriculture, and environmental sustainability challenges.

11. Connections with Health Issues

Epigenetics, the study of heritable changes in gene expression that do not involve alterations in DNA sequence, has profound implications for understanding human health issues. The field of study investigates the influence of environmental factors and lifestyle choices on gene activity, which affects subsequent generations’ health consequences [148]. This connection between epigenetics and human health is pivotal for several reasons. Epigenetic mechanisms regulate gene expression patterns critical for various physiological processes, including immune response, metabolism, and cellular differentiation [149]. Abnormal epigenetic alterations can make persons more susceptible to diseases such as cancer, cardiovascular ailments, and neurological conditions. For instance, DNA methylation alterations have been linked to the development and progression of cancers, highlighting the potential diagnostic and therapeutic implications of epigenetic research [150]. The concept of Developmental Origins of Health and Disease (DOHaD) underscores how early-life environmental exposures can affect long-term health outcomes through epigenetic modifications [151]. Adverse conditions in utero or during infancy, such as poor nutrition or exposure to toxins, can induce epigenetic changes that increase susceptibility to chronic diseases later in life [152]. The comprehension of these mechanisms can be used to develop strategies for preventive healthcare and early intervention. Moreover, epigenetic markers offer promising avenues for personalized medicine approaches. Healthcare professionals can customize treatment regimens by analyzing epigenetic patterns in people, allowing them to anticipate and address potential responses and hazards [153]. This approach holds the potential for optimizing therapies and improving patient outcomes across various diseases, including complex conditions with genetic and environmental components [154].

12. Aquaculture Infections

Aquaculture infections represent a significant challenge in the sustainable farming of aquatic organisms worldwide. These infections, caused by a variety of pathogens including viruses, bacteria, and parasites, can lead to severe economic losses and environmental impacts if not effectively managed [155]. DNA methylation involves the addition of methyl groups to DNA molecules, which can regulate gene expression [156]. In the context of aquaculture infections, DNA methylation plays a critical role in modulating immune responses and disease resistance in farmed fish (

Table 2. Primary concerns in aquaculture species over time (Epigenetic Perspective).

Year	Affected Fish Species	Epigenetic Considerations	References
2024	Common Carp	Suggested a disruption of epigenetic regulation in KHV-exposed leukocytes.	[163]
2023	Rainbow Trout	Initial studies on epigenetic reprogramming after IPNV infection in salmonid cells, demonstrating changes in promoter methylation/demethylation levels and the histone code.	[164]
2021	Atlantic Salmon	Environment-driven reprogramming of gamete DNA methylation occurs during maturation and is transmitted intergenerationally in Atlantic Salmon.	[165]
2021	Cichlid Fishes	Competing male- and female-determining genetic and hormonal networks governed by epigenetic factors.	[166]
2021	Poecilia mexicana	DMR-associated genes were related to sulfur toxicity and metabolic processes.	[167]
2022	European sea bass	DNA-methylation biomarkers linked to short-term, mid-term, long-term, and very-long-term effects of temperature in both somatic and reproductive tissues.	[168]
1984	Atlantic Salmon	Exploring epigenetic resistance to infectious salmon anemia in heart tissues.	[169]
2022	Nile tilapia	DNA methylome and RNA transcriptome during high-temperature-induced masculinization in sex-undifferentiated Nile tilapia gonad.	[170]
2022	Japanese flounder	Acute hypoxic stress at multiple metabolic levels by changing DNA methylation.	[171]
2018	Hermaphrodite barramundi	Sex-specific dmrt1 and cyp19a1 methylation and alternative splicing in gonads of the protandrous hermaphrodite barramundi.	[172]
2018	Chinese sea perch	Expression and DNA methylation analysis of cyp19a1a in Chinese sea perch Lateolabrax maculatus.	[173]
2018	Culter alburnus	Expression of zona pellucida 3 gene is regulated by 17α-ethinylestradiol in adult topmouth Culter, Alburnus.	[174]
2020	Large yellow croaker	Analysis of DNA methylation differences in gonads of the large yellow croaker.	[175]
2020	Schizothorax kozlovi	Expression Profiles of dmrt1 in Schizothorax kozlovi, and Their Relation to CpG Methylation of Its Promoter and Temperature.	[176]
2020	Pelvicachromis pulcher	Epigenetic regulation of gonadal and brain aromatase expression in a cichlid fish with environmental sex determination.	[177]
2013	ricefield eel	Epigenetic modifications during sex change repress gonadotropin stimulation of cyp19a1a in a teleost ricefield eel (Monopterus albus).	[31]
2021	Orange spotted grouper	Potential role of DNA methylation of cyp19a1a promoter during sex change in protogynous orange-spotted grouper, Epinephelus coioides.	[178]
2018	Olive flounder	Promoter methylation and Hoxd4 regulate UII mRNA tissue-specific expression in olive flounder (Paralichthys olivaceus).	[179]
2019	Oncorhynchus mykiss	Temporal Dynamics of DNA Methylation Patterns in Response to Rearing Juvenile Steelhead (Oncorhynchus mykiss) in a Hatchery versus Simulated Stream Environment.	[180]
2022	Channel Catfish	Identification of an Epigenetically Marked Locus within the Sex Determination Region of Channel Catfish.	[181]
2014	Atlantic cod	Thermal stress alters expression of genes involved in one-carbon and DNA methylation pathways in Atlantic cod embryos.	[182]
2023	Shrimp	Epigenetic Modulations for Prevention of Infectious Diseases in Shrimp Aquaculture.	[54]
2023	Cyprinus carpio	Epigenetic mechanisms of lncRNA in response to thermal stress during embryogenesis of allotetraploid Cyprinus carpio.	[183]

) [157]. Specific patterns of DNA methylation in immune-related genes have been correlated with susceptibility or resistance to various pathogens [158]. Moreover, histones are proteins that help package DNA into chromatin, and modifications to these proteins such as acetylation and methylation can alter chromatin structure and gene accessibility [159]. Histone modifications influence the transcription of genes involved in immune responses and pathogen recognition in fish. For instance, changes in histone acetylation patterns have been linked to enhanced immune defense mechanisms against viral and bacterial infections in aquaculture species [160]. Furthermore, microRNAs are small non-coding RNA molecules that regulate gene expression post-transcriptionally by binding to target messenger RNAs (mRNAs) [161]. In aquaculture infections, specific miRNAs have been identified as critical regulators of immune responses and host–pathogen interactions. These miRNAs can modulate the expression of genes involved in the immune signaling pathway, thereby influencing the susceptibility or resistance of fish to infectious diseases [162].

13. Epigenetic Factor in Fish Population Dynamics

Population dynamics are crucial for effective fisheries management and conservation efforts. Fish populations are influenced by various factors, including genetics, environment, and increasingly recognized epigenetics [184]. Epigenetic mechanisms play significant roles in regulating gene expression patterns without altering the DNA sequence, thereby impacting traits such as growth rates, reproductive success, and survival within fish populations [185]. Epigenetic modifications can affect phenotypic traits that are crucial for the survival and health of fish populations [186]. Moreover, epigenetic changes can regulate genes involved in growth hormone pathways, influencing the growth rates of individual fish within a population [187]. Variations in growth rates can impact population dynamics by affecting size distributions and productivity. Furthermore, epigenetic mechanisms play roles in reproductive processes, including gamete production and fertilization success [188]. Changes in epigenetic regulation can influence reproductive behaviors, mating success, and offspring viability, thereby shaping population structure and genetic diversity [189]. In the context of survival under stress, fish populations face numerous environmental stressors, such as pollution, habitat degradation, and climate change (Figure 3). Epigenetic modifications allow fish to adapt to these stressors by altering gene expression patterns related to stress response pathways [52]. However, prolonged exposure to stressors can lead to dysregulation of epigenetic mechanisms, potentially increasing mortality rates or reducing overall fitness within populations [190].

14. Limitations

Despite their utility, traditional approaches for studying fish health have several limitations. Clinical observations and behavioral assessments can be subjective and vary depending on the observer’s experience and interpretation. Some diseases or health issues may not present obvious external symptoms, making them difficult to detect through gross pathology or visual inspection alone [191]. Limited sample sizes in studies can affect the accuracy and generalizability of findings, especially in diverse or large fish populations [192]. Many traditional methods, such as histopathology and diagnostic testing, require significant time and expertise, which can delay timely responses in disease management [193]. Diagnostic procedures involving capture, handling, euthanasia, and tissue sampling can be invasive and may induce physiological stress in live fish, potentially affecting their health and behavior. In addition, advanced diagnostic methods and environmental monitoring may require specialized equipment, laboratory infrastructure, and technical expertise, which can increase costs and limit their accessibility in resource-limited settings [194]. Environmental factors can influence fish health outcomes, complicating the attribution of health issues solely to biological factors [195]. Traditional methods may focus on visible symptoms or specific pathogens, potentially overlooking complex intersections between multiple stressors affecting fish health [196]. Invasive procedures and stress-inducing methods raise ethical concerns regarding the welfare of fish involved in research [197]. Addressing these limitations often involves integrating traditional methods with emerging technologies and interdisciplinary approaches. Advances in molecular biology, remote sensing, and non-invasive monitoring techniques offer opportunities to enhance the accuracy, efficiency, and ethical standards of fish health assessments in the future.

15. Epigenetics in Aquaculture and Its Importance

Epigenetics refers to heritable changes in gene expression that do not involve alterations to DNA sequence itself. In recent years, epigenetic research has gained prominence in understanding the mechanisms underlying fish health, particularly in the context of aquaculture and toxicology. Aquaculture, the farming of fish and other aquatic organisms, plays a crucial role in meeting global demand for seafood while alleviating pressure on wild fish stocks [198]. However, genetic limitations can hinder aquaculture production and contribute to challenges such as disease outbreaks and environmental variability [199]. Epigenetic mechanisms such as DNA methylation, histone modifications, and non-coding RNAs play pivotal roles in regulating gene expression in response to environmental stimuli. These mechanisms can influence traits important for aquaculture production, including growth rates, disease resistance, stress tolerance, and reproductive success [199].

15.1. Growth and Development

Studies have shown that epigenetic modifications can affect growth-related genes in fish, impacting growth rates and body size [200]. For instance, altered DNA methylation patterns have been linked to variations in growth trajectories among fish populations subjected to different environmental conditions in aquaculture settings [201]. This could lead to targeted breeding strategies aimed at enhancing growth performance in commercially important species.

15.2. Disease Resistance and Immune Function

Disease outbreaks pose significant threats to aquaculture sustainability [202]. Epigenetic research has provided insight into the way fish change immune-related genes in response to infections and environmental stimuli [203]. Enhanced understanding of epigenetic regulation of immune function could facilitate the development of disease-resistant fish strains through selective breeding or epigenetic modification strategies.

15.3. Stress Responses

Fish in aquaculture are exposed to various stressors such as handling, transport, changes in water quality, and crowding [204]. Epigenetic research has identified stress-responsive genes and pathways regulated by epigenetic mechanisms, offering potential avenues for improving stress resilience in farmed fish [205]. Strategies focusing on mitigating stress-induced epigenetic changes could enhance overall welfare and productivity in aquaculture operations [200].

15.4. Epigenetics in Fish Toxicology

Fish are excellent bioindicators of environmental pollution due to their direct exposure to aquatic contamination [206]. The primary objective of toxicological research on fish is to comprehend the effects of pollutant substances, such as pesticides, industrial chemicals, pharmaceuticals, and heavy metals [207]. Epigenetic mechanisms provide insights into the molecular responses of fish to environmental contaminants and show promise as biomarkers for environmental monitoring and chemical hazard and risk assessment [208].

15.5. Epigenetic Responses to Environmental Contaminants

Exposure to environmental pollutants can induce epigenetic changes in fish, altering gene expression patterns associated with detoxification pathways, oxidative stress responses, and immune function [124]. For example, studies have demonstrated DNA methylation changes involved in detoxification processes in fish exposed to heavy metals such as mercury and cadmium. These epigenetic alterations can influence susceptibility to toxicity and contribute to adverse health effects in fish populations [209].

15.6. Impact on Reproductive Health

Environmental contaminants can disrupt the reproductive process in fish through epigenetic mechanisms [210]. Disrupted DNA methylation patterns in genes critical for reproductive development and hormone regulation have been observed in fish exposed to endocrine-disrupting chemicals (EDCs). These findings underscore the potential long-term effects of contaminants on fish reproductive health and population sustainability [211].

15.7. Ecotoxicogenomics and Integrated Approaches

Epigenetic studies complement traditional ecotoxicological approaches by providing mechanistic insights into molecular pathways underlying pollutant-induced toxicity in fish [212]. Integrated approaches combining epigenetics with genomics, transcriptomics, proteomics, and metabolomics offer comprehensive assessments of environmental stressors on fish health and ecosystem dynamics [121]. These multidisciplinary approaches enhance the predictive power of ecotoxicological research and support evidence-based environmental management strategies. Epigenetic biomarkers have emerged as valuable tools for environmental monitoring and conservation efforts [213]. Researchers can detect early signs of environmental stress and ecosystem degradation by assessing epigenetic profiles in wild populations [214]. Epigenetic markers also hold promise for assessing the efficacy of habitat restoration initiatives and evaluating the long-term impacts of anthropogenic activities on aquatic biodiversity [215].

15.8. Effects of Environmental Factors on Epigenetic Regulation

Environmental factors are important modulators of epigenetic regulation in fish and can influence physiological processes, development, stress responses, immune function, reproduction, and disease susceptibility [9]. In aquaculture and natural aquatic ecosystems, fish are exposed to multiple environmental stressors, including ultraviolet (UV) radiation, changes in temperature and pH, hypoxia, heavy metals, pesticides, petroleum-derived compounds, and other chemical contaminants [216]. These stressors can modify epigenetic processes, including DNA methylation, histone modifications, and non-coding RNA-mediated gene regulation, thereby altering transcriptional responses and potentially influencing long-term phenotypic outcomes [217].

UV radiation represents an important environmental stressor because excessive exposure can induce DNA damage and activate cellular DNA-repair and stress-response pathways [218]. UV-induced cellular stress may be accompanied by changes in DNA methylation, chromatin-associated mechanisms, and microRNA expression [219]. However, evidence directly linking UV-induced epigenetic alterations to melanoma development in fish remains limited compared with the extensive evidence available from human and mammalian cancer research [220]. Therefore, the relevance of these mechanisms to fish pigment-cell disorders and melanoma-like conditions should be considered an emerging area requiring further investigation.

Aquatic contaminants can also interfere with epigenetic regulation in fish. Heavy metals, including cadmium, arsenic, lead, and other contaminants, have been reported to alter DNA methylation and non-coding RNA profiles in fish [221]. Such changes may affect genes involved in oxidative stress, metabolism, immune responses, development, and cellular homeostasis [222]. Importantly, these studies demonstrate environmental epigenetic effects but do not necessarily establish a direct causal relationship between contaminant-induced epigenetic changes and melanoma. Consequently, their potential contribution to pigment-cell dysfunction or tumor-related processes should be interpreted cautiously [223].

Organic contaminants, including polycyclic aromatic hydrocarbons (PAHs), pesticides, and petroleum-associated compounds, may similarly influence epigenetic regulation through alterations in DNA methylation, histone-associated chromatin regulation, and microRNA expression. These mechanisms can modify transcriptional responses to environmental stress and may contribute to disease susceptibility when exposure is prolonged or occurs during sensitive developmental stages. In aquaculture systems, understanding these interactions is particularly important because chronic exposure to environmental contaminants may interact with nutritional, thermal, hypoxic, and infectious stresses [224].

Overall, environmental epigenetics provides an important framework for understanding how external stressors can influence fish health beyond immediate physiological responses (

Table 3. Impact of environmental factors on melanoma via epigenetic mechanisms in various fish species.

Environmental Factor	Fish Species	Epigenetic Mechanism	Influence on Melanoma	Reference
UV Radiation	Zebrafish	DNA Methylation	Promotes hypermethylation of tumor suppressors	[226]
Chemical Pollutants	Medaka	Histone Modifications	Induces alterations in chromatin structure	[227]
Temperature Fluctuations	Trout	Non-coding RNAs	Alters expression of lncRNAs involved in melanogenesis	[228]
pH/Alkalinity Stress	Tilapia	miRNA expression changes and altered post-transcriptional regulation	Alters miRNA-mediated stress and ionoregulatory pathways; a direct link with melanoma has not been established	[229]
[229]Hypoxia	Salmon	Chromatin Remodeling	Facilitates changes in chromatin accessibility	[230]
Diet	Zebrafish	DNA Demethylation	Influences global DNA methylation patterns	[231]
Infection	Medaka	Histone Acetylation	Modulates expression of immune-related genes	[232]
Metal Contamination	Tilapia	DNA Hydroxymethylation	Alters epigenetic landscape	[233]
Noise Pollution	Salmon	miRNA Biogenesis	Disrupts processing of precursor miRNAs	[234]
Radiation Exposure	Medaka	Chromatin Accessibility	Modulates DNA accessibility at regulatory regions	[235]
Endocrine Disruptors	Trout	Non-coding RNA Expression	Dysregulates lncRNA networks implicated in melanoma	[236]
Microplastic Pollution	Tilapia	miRNA Targeting	Alters miRNA interactions with target mRNAs	[237]
Pharmaceutical Residues	Salmon	Histone Phosphorylation	Influences transcriptional activity	[238]
Solar Radiation	Zebrafish	DNA Methylation	Leads to alterations in promoter methylation patterns	[239]
Heavy Metal Exposure	Medaka	Histone Acetylation	Induces modifications linked to gene expression changes	[240]
Heat Stress	Tilapia	miRNA Biogenesis	Impacts miRNA processing machinery	[241]
Benzo[a]pyrene exposure	Zebrafish	Global DNA hypomethylation and promoter-specific DNA demethylation	Potential disruption of epigenetic regulation; direct melanoma induction was not demonstrated	[242]
Algal Blooms	Carp	miRNA Dysregulation	Modulates miRNA expression profiles	[243]
Air Pollution	Zebrafish	DNA Methylation	Leads to aberrant DNA methylation patterns	[244]
Oil Spills	Medaka	Histone Acetylation	Disrupts normal histone acetylation levels	[245]
Perfluorononanoic Acid (PFNA)	Zebrafish	Chromatin Accessibility	Affects DNA accessibility and gene expression	[246]
Noise Pollution	Medaka	DNA Methylation	Leads to alterations in DNA methylation patterns	[227]
Chemical	Trout	Histone Modifications	Impacts chromatin structure and gene regulation	[247]
Unknown	Tilapia	Non-coding RNA Expression	Dysregulates expression of lncRNAs involved in melanoma	[248]
Copper	Zebrafish	miRNA Biogenesis	Affects miRNA processing and maturation	[249]
Phosphate	Zebrafish	DNA Demethylation	Modulates DNA demethylation processes	[250]
Pesticide Use	Medaka	Histone Acetylation	Alters histone acetylation levels
Alkalinity Stress Tolerance	Tilapia	miRNA Dysregulation	Influences miRNA expression and function	[251]
Ionizing Radiation	Zebrafish	Histone Methylation	Impacts histone methylation patterns	[252]
Plastic Waste	Zebrafish	Chromatin Remodeling	Induces changes in chromatin structure	[253]
Glyphosate	Medaka	DNA Methylation	Alters DNA methylation patterns	[254]
Ocean Acidification	Seabream	Histone Acetylation	Modulates histone acetylation levels	[255]
Industrial Waste	Tilapia	Non-coding RNA Expression	Dysregulates expression of regulatory lncRNAs	[256]
Arsenic	Salmon	miRNA Targeting	Alters miRNA interactions with mRNA targets	[257]
Bisphenol A (BPA)	Zebrafish	DNA demethylation/global DNA hypomethylation	Reduced global DNA methylation and altered expression of dnmt1, dnmt3s and tet genes	[258]
Mining Activities	Medaka	Histone Modifications	Induces changes in histone modification patterns	[259]
Freshwater-to-seawater transition (smoltification)	Salmon	Histone acetylation (H3K9ac)	H3K9ac decreases following seawater transfer, accompanied by increased HDAC1 expression, suggesting histone acetylation contributes to transcriptional regulation during smoltification	[260]

). Nevertheless, the available evidence varies considerably among environmental factors, fish species, tissues, and epigenetic mechanisms [225]. Future studies should therefore integrate controlled exposure experiments with genome-wide DNA methylation, histone-mark profiling, and non-coding RNA analyses to determine whether environmentally induced epigenetic changes are transient adaptive responses or persistent alterations associated with disease phenotypes. Such approaches may also help clarify whether epigenetic dysregulation contributes directly to pigment-cell abnormalities or melanoma development in fish.

16. Contaminants of Emerging Concern

Contaminants of emerging concern (CECs) refer to pollutants that have been identified or are gaining attention due to their potential environmental and health impacts. Pharmaceuticals, personal care items, insecticides, industrial chemicals, microplastics, and nanomaterials are a few examples [261]. It is imperative to comprehend the impact of CECs on aquatic ecosystems and organisms, such as salmon, to ensure the preservation of public health and environmental management [262]. There are several key future directions and applications.

16.1. Identification of Epigenetic Biomarkers

Researchers are increasingly focusing on identifying epigenetic biomarkers that can serve as indicators of CEC exposure and its effects on fish. Biomonitoring tools can assess environmental health and detect early signs of ecosystem disruption through the profiling of epigenetic changes due to specific contaminants such as pharmaceuticals or microplastics [263]. Moreover, epigenetic changes induced by CEC exposure in one generation of fish can be inherited by subsequent generations, potentially affecting population dynamics and evolutionary trajectories. Transgenerational epigenetic inheritance helps elucidate the adaptive responses of fish to environmental stressors and informs strategies for sustainable fisheries management and conservation [264]. Furthermore, epigenetic research contributes to evidence-based decision-making in environmental regulation and policy development. Researchers can advocate for stricter regulations, pollution prevention measures, and sustainable management practices to mitigate environmental contamination and protect aquatic biodiversity [265].

16.2. Mechanistic Understanding of CEC Effects

Contaminants of Emerging Concern (CECs) present significant challenges to both environmental and fish health due to their novel and often inadequately regulated nature [266]. These substances include pharmaceuticals, personal care products, industrial chemicals, and other synthetic compounds that are increasingly found in various environmental matrices [267]. Mechanistically, CECs can impact biological systems through several pathways. They often interact with cellular receptors, leading to endocrine disruption by mimicking or blocking natural hormones, thereby altering physiological processes [268]. Enzymatic pathways can also be disrupted, either through inhibition, which results in the accumulation of toxic metabolites, or through induction, which may enhance the metabolism of other compounds [269]. Additionally, CECs can induce genetic and epigenetic changes, such as alterations in DNA methylation and histone modification, influencing gene expression and contributing to diseases like cancer [142]. At the cellular level, these contaminants can generate oxidative stress by producing reactive oxygen species, disrupting cellular homeostasis, and affecting critical signaling pathways. These disruptions can manifest as developmental and reproductive effects, neurotoxicity, and immune system modulation [270]. The impacts extend to entire organisms and ecosystems, where CECs can cause developmental abnormalities, reproductive failures, behavioral changes, and ecosystem health deterioration.

16.3. Future Perspectives: AI-Driven Epigenetics in Fish Health

Future advances in artificial intelligence, deep learning, and big-data analytics are expected to revolutionize fish health research and aquaculture management. Integrating machine learning with multi-omics data will enable predictive modeling of disease susceptibility and environmental stress responses in fish populations. AI-driven decision-support systems could assist aquaculture producers in monitoring water quality, predicting pathogen outbreaks, and optimizing feeding strategies. In addition, combining epigenetic biomarkers with environmental data may improve conservation efforts by identifying populations that are more resilient to climate change and environmental disturbances. Developing collaborative frameworks between molecular biologists, data scientists, and aquaculture specialists will be essential for translating these technological advances into practical applications for sustainable fisheries and ecosystem management.

17. Conclusions

Environmental stressors can substantially influence fish physiology, development, reproduction, immunity, and survival, with epigenetic mechanisms such as DNA methylation, histone modifications, chromatin remodeling, and non-coding RNAs contributing to these responses. Advances in high-throughput sequencing, multi-omics, and bioinformatics have improved our understanding of these regulatory processes and their potential relevance to environmental adaptation and aquaculture. However, many reported epigenetic changes remain associative, and their causal roles in phenotypic plasticity, acclimation, adaptation, and transgenerational inheritance require further validation.

Machine learning and predictive modeling offer promising approaches for analyzing complex epigenomic datasets, but their application in fish remains relatively limited and is largely focused on DNA methylation-based prediction. Therefore, their broader application in aquaculture and environmental management should be considered an emerging opportunity rather than an established practice. Future research should emphasize functional and multigenerational validation of candidate epigenetic markers, standardized and longitudinal studies across diverse fish populations, and independent validation of computational models. Integrating epigenomic, genomic, transcriptomic, physiological, and environmental data may ultimately improve our understanding of fish responses to environmental change and support the development of reliable applications in sustainable aquaculture and aquatic ecosystem management.