Mytilus galloprovincialis, Mediterranean mussel, is a shellfish species of great economic and ecological importance, and knowledge about the microbiome of this species is important for understanding its physiology and health in different conditions for the purpose of biomonitoring and predicting the response to climate change. As filter feeders, mussels accumulate microbial organisms from the environment, making them an integral part of mussel physiology and can endow the host with a set of functions like resistance to pathogens, improvement of immune response, detoxification mechanisms, but can also be sources of disease. In this research, the total microbial community in tissues (gills and hepatopancreas) of farmed mussels and marine water of the Krka River estuary during 2022/2023. was analyzed by DNA metabarcoding method, using the V4-V5 variable region of the 16S rRNA gene. The bioinformatic analyses of the obtained data revealed the greatest abundance of Proteobacteria, Bacteroidota and Firmacutes in tissues with significant seasonal differences. Out of a total of 648 identified genera, 522 were recorded in gills, 516 in hepatopancreas and 498 in the sea, and of these 331 genera appeared in all three types of samples. Of the genera that include pathogenic organisms, Vibrio, Clostridium, and a group designated as Escherichia-Shigella were recorded, but with very low abundance and always in hepatopancreas. The highest alpha diversity was recorded for water samples, and the lowest for gills and hepatopancreas, on the other hand according to community composition, seawater samples were the most homogeneous group.