First described in the 19th century, Aeromonas salmonicida subsp. salmonicida (hereafter A. salmonicida) is one of the oldest known fish pathogens, responsible for the furunculosis diseases in salmonid fish. A. salmonicida is an important pathogen due to its nearly worldwide distribution, broad host range and potentially devastating impacts on wild and farm fish. A. salmonicida chromosome is unstable, and after thermal shock, the A. salmonicida genome is modified by endogenous insertion sequences (IS). The mechanisms and the whole genome modification, and their effect on virulence and physiology are unknown. In this study, we sequence the whole genome of A. salmonicida J223 and high virulent strain and compared to other A. salmonicida genomes. Additionally, we used RNA-sequencing of A. salmonicida under heat shock to determine the mechanism of endogenous mutagenesis. Finally, we sequenced the whole genome of A. salmonicida strains isolated after endogenous mutagenesis. Here, we provided with novel insight of A. salmonicida virulence evolution and the impact of climate change on marine bacterial pathogens.