Abstract

In the context of increasing freshwater scarcity and the effects of climate change on aquatic environments, developing salt-tolerant fish strains has become a critical strategy for sustainable aquaculture. The limited availability of suitable species for saline-water aquaculture poses a significant challenge, severely impacting the development of the fishery economy. This study investigated the effects of 24 h exposure to freshwater, and seawater at salinities of 4, 9 ppt and 12 ppt, on juvenile grass carp ( Ctenopharyngodon idella ). Following these exposures, liver tissues were collected to assess physiological and biochemical indicators, as well as transcriptional and metabolic responses. Histological examination revealed that liver structure was compromised after 24 h of exposure to 9 ppt and 12 ppt salt stress. Concurrently, we observed a decrease in the levels of Superoxide Dismutase (SOD), whereas the levels of Malondialdehyde (MDA) exhibited an increase. Salinity exposure significantly altered the levels of 120 metabolic products (67% of which were lipid and lipophilic molecules) and the transcriptional expression of 1005 genes. Metabolomic analysis indicated that most of the significantly different metabolites were associated with the metabolism of lipids and amino acids. Transcriptome analysis revealed significant enrichment of 20 metabolic pathways, including glutathione metabolism, lipid digestion and absorption, bile secretion, glycerolipid metabolism, and the tricarboxylic acid cycle. Comprehensive multi-omics analysis revealed significant alterations in key metabolic pathways, including glycerophospholipid metabolism, α-linolenic acid metabolism, histidine metabolism, and β-alanine metabolism, along with several vital genes such as HO-1, NQO1, GCLM, and GSS, under salt stress. These changes closely correlate with variations in cellular membrane lipid composition and antioxidant activity. Further analysis demonstrated that acute salt stress induce