Transcriptomic Landscape of Gut Microbiota–Host Interactions Reveals Domestication-Related Changes in the Pearl Oyster Pinctada maxima

The offspring of domesticated Pinctada maxima exhibited various physiological and microbial adjustments to the complex and dynamic conditions of coastal environments. To support the restoration of P. maxima genetic resources and explore the molecular mechanisms underlying these phenotypic responses, we conducted a comparative analysis of the intestinal transcriptome and microbiota of wild parental and domesticated generations. Each sample generated an average of 43,600,525 clean reads, which were mapped to the P. maxima reference genome with mapping rates ranging from 63.91% to 79.48%, and a total of 3007 differentially expressed genes (DEGs) were subsequently identified. Gene Ontology analysis revealed that the DEGs were enriched in organic acid metabolism, and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that the DEGs were enriched in glycosphingolipid biosynthesis and xenobiotic metabolism via cytochrome P450. Microbiota profiling revealed significant compositional shifts at phylum and genus levels, with increased alpha diversity in F1; dominant phyla transitioned towards Spirochaetota and Bacteroidota, and functional predictions pointed to enhanced metabolic and immune capacities. Quantitative validated the up-regulation of immune genes (PmHR96h, PmIAP) and down-regulation of calcium-signaling genes (PmCaM, PmHSP90), consistent with RNA-seq data. Collectively, these coordinated transcriptomic and microbial alterations reflect a multifaceted host–microbiome adaptive response to nearshore conditions. Our findings provide valuable molecular markers and microbial indicators for selective breeding and health monitoring, offering a scientific basis for improving the resilience of P. maxima aquaculture under changing environmental conditions.