Recently, it has been demonstrated that the Pacific oyster mortality syndrome affecting Crassostrea gigas oysters is caused by multiple infection with an initial and necessary step of infection by the Ostreid herpesvirus type 1. Here we extend the concept of this pathobiome beyond the host species and its bacterial microbiota by investigating how seaweed communities living around oysters influence their response to the disease. It has been found that seaweeds can alter the microbiota of the host and its response to the disease by modifications of its transcriptional immune response, leading to increased susceptibility to the disease. This work provides a better understanding of a marine disease and highlights the importance of considering both macro and microbiotic interactions for conservation, management, and exploitation of marine ecosystems and resources.