Abstract: Coral diseases are significant drivers of global coral reef degradation. Although extensive researches have described coral diseases, the occurrence, progression, and underlying molecular mechanisms remain incompletely understood. This study elucidates the molecular mechanisms underlying disease progression in Montipora foliosa through integrated transcriptomic profiling of the coral host and comprehensive analysis of microbial community dynamics in coral-associated bacteria. The study evaluated three distinct tissue stages of coral disease: healthy, intermediate, and lesioned tissues. Microbial communities analysis revealed that the healthy coral tissues were predominantly composed of Proteobacteria, Firmicutes, Bacteroidota, and Actinobacteriota. In the lesioned tissues, the diversity of associated bacterial communities decreased, with an increase in the relative abundance of Proteobacteria and Campilobacterota, and a decrease in Firmicutes, Bacteroidota, and Actinobacteriota. Proteobacteria predominated in both healthy and diseased corals, with relative abundance increasing with disease severity. Notably, the elative abundance of microbial taxa such as Vibrio, Shimia, and Ruegeria showed increased abundance, suggesting these communities may adapt to the occurrence of such diseases and serve as potential pathogens. In the lesioned tissues, the concentration of Vibrio was significantly higher than in the healthy tissues. Two unclassified Vibrio species (OTU-17, OTU-231) may be the main pathogenic microorganisms of this coral disease. Transcriptomic analysis of the coral host revealed significant downregulation of genes involved in cell adhesion, surface receptor signaling, immune-related signaling pathways, and ion transport during disease progression, reflecting immunosuppression. In conclusion, distinct shifts in microbial communities and transcriptomic responses of coral holobionts were observed across different stages of coral disease, providing a theoretical foundation for understanding the onset and progression of coral diseases in coral aquarium cultures.