Multi-omics analysis reveals organ-specific oxidative stress, apoptosis, and ferroptosis-related signatures in Macrobrachium rosenbergii under ammonia–hypoxia co-stress

) under normoxia and hypoxia. Survival decreased precipitously with escalating TAN and oxygen depletion, evidencing combined effects on lethality. Histopathology revealed hepatopancreatic tubular disintegration, gill lamellar collapse, and myofibrillar fragmentation. Antioxidant defenses (SOD, CAT, GSH) decreased, while MDA accumulated, reflecting intensified lipid peroxidation. Transcriptomics showed cross-organ activation of glutathione metabolism, ferroptosis-associated pathways, oxidative phosphorylation, and apoptosis, pointing to mitochondrial redox failure. Weighted gene co-expression analysis identified MAP3K1, HSPA1, ENO, and GAPDH as key stress regulators. Gill metabolomics revealed remodeling of TCA cycle intermediates, amino acids, and phospholipids under combined high TAN-low DO. Overall, ammonia-hypoxia co-stress induced mitochondrial dysfunction, redox imbalance, and structural damage, with the hepatopancreas being most vulnerable. These findings clarify the molecular pathology of nitrogen-oxygen co-stress and inform environmental threshold management for crustacean aquaculture.