Development of transcriptional biomarkers for ammonia stress in fish

Abstract Ammonia loading is recognized as a pervasive constraint in intensive aquaculture and eutrophic waters, yet transcriptional indicators of ammonia stress have been reported across disparate species, tissues, and exposure regimes. In this review, fish studies linking ammonia exposure to mRNA responses are synthesized using a tissue-forward framework that prioritizes first-contact epithelia and downstream metabolic organs. In gills, recurring modulation is described for Rhesus glycoproteins, particularly Rhbg and Rhcg / RhCG isoforms, and associated acid–base and ionoregulatory machinery (V-type H + -ATPase, Na + /H + exchangers, carbonic anhydrase, Na + /K + -ATPase), alongside inflammatory and remodeling signals consistent with epithelial disturbance. In liver and other internal tissues, coherent shifts are reported in amino-acid and nitrogen metabolism, mitochondrial energy pathways, redox control, and cell-death programs, with representative candidate biomarkers including glutamine synthetase, carbamoyl phosphate synthetase I, antioxidant/redox genes, cytokine-related markers, and apoptosis/ferroptosis-associated transcripts. Because many oxidative and immune transcripts are shared among stressors, improved diagnostic value is expected when biomarker panels are derived from co-regulated modules using network-guided reduction approaches, including weighted gene co-expression network analysis (WGCNA), and validated against key confounders. Candidate gene sets are collated and a roadmap is outlined for translating tissue signatures into compact assays for aquaculture management and field surveillance.