Integrative omics elucidates the hepatopancreatic protective effects of Origanum vulgare-derived phenolic compounds via lipid remodeling and detoxification enhancement in Procambarus clarkii.

Although oregano phenols (carvacrol and thymol) derived from Origanum vulgare are known antioxidants, their molecular impact on the crustacean hepatopancreas remains unclear. We characterized the molecular and metabolic changes in the hepatopancreas of Procambarus clarkii using an integrative omics approach. A 60-day trial compared control and oregano-treated groups using histology, transcriptomics (RNA-Seq), and non-targeted metabolomics (LC-MS/MS). Histology showed enhanced tissue structure and increased R-cell abundance. Integrated omics identified 2,236 differentially expressed genes and significant thymol/thymol sulfate accumulation. The concurrent upregulation of ribosome biogenesis and accumulation of nucleotides indicated enhanced protein synthesis capacity. Notably, we characterized the selective downregulation of Phase I metabolic genes and the robust upregulation of Phase II detoxification enzymes; concentrated upregulation of Phase II enzymes (SULTs, UGT5, GSTs) was consistent with enhanced conjugation and clearance of xenobiotic metabolites, although direct evidence for reduced oxidative damage was not obtained. Furthermore, downregulated bacterial invasion and Toll-like receptor pathways indicated substantial remodeling of immune-related transcriptional programs rather than a straightforward enhancement of disease resistance. Oregano phenols optimize hepatopancreatic function by coordinating detoxification, protein synthesis, and lipid networks. Our findings elucidate the specific regulatory mechanisms of oregano phenols as functional feed additives to enhance resilience and hepatopancreatic function in sustainable aquaculture.