Multi-Omics Analysis of Hepatopancreatic Responses to Ammonia Nitrogen Stress in Diploid Pacific Oysters (Magallana gigas).

Ammonia nitrogen represents a critical environmental stressor in aquaculture and exerts adverse impacts on the growth, reproduction and survival of shellfish. In the present study, diploid Pacific oysters (Magallana gigas) were exposed to ammonia nitrogen stress for 0, 6, and 48 h. We combined histopathological examination, antioxidant enzyme measurements, transcriptome profiling, and metabolome profiling to characterize time-dependent hepatopancreatic responses. Tissue injury became progressively more severe with prolonged exposure. Superoxide dismutase activity increased throughout the experiment, whereas catalase and glutathione peroxidase activities and malondialdehyde content showed an increase followed by a decrease, with no statistically significant differences in malondialdehyde content among the three time points. Transcriptome data revealed alterations in genes associated with ATP-binding cassette transporters, lysosomal function, endocytosis, and autophagy. Metabolic alterations were mainly associated with nucleotide, purine, pyrimidine, and sphingolipid metabolism. Cross-omics integration linked these molecular shifts to transmembrane transport, glutathione metabolism, sulfur-containing amino acid metabolism, and amino acid biosynthesis. The consistency between transcriptomic and metabolomic signals further highlights the central roles of transport processes, antioxidant defense, and metabolic adjustment under ammonia nitrogen exposure. These findings indicate that diploid Pacific oysters respond to ammonia nitrogen stress through coordinated regulation of oxidative stress responses, transmembrane transport, intracellular degradation and clearance, and metabolic reorganization. These findings provide insights into the adaptive mechanisms of bivalves exposed to ammonia nitrogen stress.