Histological and Transcriptomic Profiling Reveals Metabolic and Immune Responses to Ammonia Stress in Scatophagus argus

Ammonia is widely regarded as the primary chemical pollutant responsible for fish toxicity in aquaculture. Scatophagus argus is an economically important euryhaline species extensively cultured in marine aquaculture. To investigate its physiological responses and molecular mechanisms under ammonia exposure, we determined the 96 h median lethal concentration (LC₅₀-96 h) of total ammonia nitrogen (TAN) for S. argus juveniles. Histopathological analyses were conducted at TAN concentrations of 0 (control), 30, and 60 mg/L, with transcriptomic analysis performed at 0 and 60 mg/L. The results showed that the LC₅₀-96 h for S. argus was 59.43 mg/L. Histological analysis revealed lamellar epithelial detachment and hepatocyte vacuolization in S. argus exposed to 60 mg/L TAN, indicating substantial structural impairment under ammonia stress. Transcriptomic profiling identified 245 differentially expressed genes (DEGs), comprising 142 upregulated and 103 downregulated genes. KEGG enrichment analysis indicated that DEGs were primarily enriched in energy metabolism and immune-related pathways. Key genes involved in glucose metabolism, amino acid metabolism, and cellular regulation (e.g., PFKM, PGM1, MAT2A, DDIT4) were significantly upregulated in energy metabolism pathways. In immune-related pathways, immune regulatory genes such as GIMAP4 and ARRDC3 were upregulated, while NAMLAA, associated with inflammatory modulation, was downregulated. Collectively, these transcriptional changes suggest that S. argus responds to external ammonia stress through coordinated regulation of energy metabolism and immune function. This study provides novel insights into the physiological and molecular strategies employed by S. argus in response to ammonia toxicity, offering a reference for environmental risk assessment and aquaculture management.