show Abstracthide AbstractRecent studies have unveiled the deep sea as a rich biosphere, populated by species descended from shallow-water ancestors post-mass extinctions. Research on genomic evolution and microbial symbiosis has shed light on how these species thrive in extreme deep-sea conditions. However, early adaptation stages, particularly the roles of conserved genes and symbiotic microbes, remain inadequately understood. This study examined transcriptomic and microbiome changes in shallow-water mussels Mytilus galloprovincialis exposed to deep-sea conditions at the Site-F cold seep in the South China Sea. Results reveal complex gene expression adjustments in stress response, immune defense, homeostasis, and energy metabolism pathways during adaptation. After 10 days of deep-sea exposure, shallow-water mussels and their microbial communities closely resembled those of native deep-sea mussels, demonstrating host and microbiome convergence in response to adaptive shifts. Notably, methanotrophic bacteria, key symbionts in native deep-sea mussels, emerged as a dominant group in the exposed mussels. Host genes involved in immune recognition and endocytosis correlated significantly with the abundance of these bacteria. Overall, our analyses provide insights into adaptive transcriptional regulation and microbiome dynamics of mussels in deep-sea environments, highlighting the roles of conserved genes and microbial community shifts in adapting to extreme environments. Overall design: In the present study, we conducted an experiment on shallow-water mussels (Mytilus galloprovincialis) at a depth of 1,119 meters in the South China Sea, as the short and mid-term simulation of the adaption process of shallow sea mussels into deep sea environments, aiming to deeply explore the deep-sea adaptation mechanism of the mussels. Both in situ deep-sea experiments and in situ sample fixation were performed to maximize the most primitive transcriptional and metagenomic changes of the organism due to deep-sea adaptation.