To improve understanding of the pathobiology of highly pathogenic avian infuenza virus (HPAIV) infections in wild birds, pathogenicity and transmissibility of HPAIV H5N8 subtype clade 2.3.4.4b was evaluated in~8-week-old herring gulls (Larus argentatus) divided into 3 groups: naïve birds (group A), birds previously exposed to low pathogenic avian infuenza virus (LPAIV) H5N1 (group B) and LPAIV H13N6 (group C). The HPAIV H5N8 virus was highly virulent for naïve gulls, that showed early morbidity, high mortality, a broad spectrum of clinical signs, including violent neurological disorders, systemic distribution of the virus in organs accompanied by high level of shedding and transmission to contact birds. Pre-exposure to homologous and heterologous LPAIV subtypes conferred only partial protection: we observed increased survival rate (statistically signifcant only in group B), nervous signs, pantropic distribution of virus in organs, shedding (signifcantly reduced in gulls of group C in the early phase of disease and asymptomatic shed‑ ding in the late phase), transmission to contact gulls (more pronounced in group B) and near-complete seroconver‑ sion in survivors. Histopathological and immunohistochemical results indicate virus tropism for the neural, respiratory and myocardial tissues. In conclusion, we demonstrate that HPAIV H5N8 clade 2.3.4.4b is highly virulent and lethal for fully susceptible herring gulls and that pre-exposure to homo- and heterosubtypic LPAIV only partially modulates the disease outcome.