Multi-omics reveals hepatopancreatic oxidative injury and detoxification mechanisms in Meretrix meretrix under acute ammonia exposure

Total ammonia nitrogen (TAN) is a reactive nitrogen contaminant that can accumulate in intensive shellfish culture and coastal benthic habitats, yet the mechanisms linking acute TAN toxicity to hepatopancreatic injury and detoxification in marine bivalves remain unclear. The hard clam Meretrix meretrix was exposed to a TAN concentration gradient to determine acute tolerance and subsequently challenged for 96 h at an LC50-level TAN concentration for antioxidant, histopathological, transcriptomic, untargeted metabolomic and RT-qPCR analyses. The 96 h LC50 was 11.686 mg L-1 TAN (95% CI, 5.543–16.195 mg L-1). TAN exposure induced an early increase in T-SOD, CAT and GSH-Px activities followed by progressive decline, whereas MDA accumulated at the late stage; hepatopancreatic and gill tissues also showed clear structural injury. RNA sequencing identified 1,317 differentially expressed genes, and metabolomics detected 444 significantly altered metabolic features. Integrated analyses converged on glutathione metabolism, sulfur metabolism, cysteine and methionine metabolism, peroxisome-related processes, ABC transporters and lysosome-associated pathways. RT-qPCR confirmed the RNA-seq trends of Gpx2, Gsto2, LGMN, SAA2, TST, SQOR and ABCC1. Together, the results indicate that acute ammonia toxicity involves early antioxidant compensation followed by oxidative injury, sulfur–glutathione redox remodeling, transporter-mediated detoxification and damage clearance. Because omics profiles were obtained from survivors after an LC50-level challenge, these responses are interpreted as survival-associated mechanisms within an acute hazard model. The findings provide mechanistic evidence for ammonia toxicity in a benthic marine bivalve and identify candidate pathways for environmental hazard assessment.