Integrated Analysis of Histophysiological Responses and Transcriptome–Metabolome Mechanisms in Coelomactra antiquata Under Ammonia Nitrogen Stress

<i>Coelomactra antiquata</i>, a marine bivalve of high nutritional and economic value, lacks comprehensive data on its toxic responses and adaptive mechanisms to ammonia nitrogen. This study integrated histophysiology, transcriptomics, and metabolomics to investigate its ammonia tolerance and molecular mechanisms, determining a 48 h LC₅₀ of 99.06 mg/L and a sublethal concentration of 9.91 mg/L. After 48 h of sublethal ammonia stress, SOD, CAT, GLDH, and GS activities in gill and hepatopancreas significantly increased, with notable changes in MDA, Gln, and urea contents, confirming disruption of antioxidant defense and nitrogen metabolism homeostasis. Tissue sections revealed irreversible histopathological damage to key tissues. Omics analyses identified 7823 differentially expressed genes (DEGs) and 737 differentially expressed metabolites (DEMs) in hepatopancreas. DEGs were enriched in metabolic pathways and multiple immune-related signaling pathways (e.g., NF-kappa B, RIG-I-like receptor), while DEMs were primarily involved in processes such as protein digestion/absorption, aminoacyl-tRNA biosynthesis, and amino acid metabolism. Research data indicate that ammonia nitrogen stress primarily regulates the antioxidant function and nitrogen metabolism homeostasis of <i>C. antiquata</i> by activating multiple immune- and metabolism-related pathways. This first systematic multi-omics study elucidates <i>C. antiquata</i>'s tolerance to ammonia nitrogen and its molecular responses, filling a gap in environmental toxicology research for sustainable aquaculture and genomic studies.