Avian influenza (AI), especially H5Nx viruses of clade 2.3.4.4b gained global attention due to their rapid evolution and widespread circulation. The infection by this clade have been documented in mammals held in captivity and the wild, together with confirmed human cases, which suggest its expansion of host range. Using the guinea pig as an in vivo transmission model, this study examined the susceptibility, viral shedding, and in-contact transmission of H5N1 virus isolate (A/duck/India/11TR05/2021) belonging to clade 2.3.4.4b. Six guinea pigs (infection subgroup) were given an intranasal dose of 106 EID50, and another six naive guinea pigs (transmission subgroup) were co-housed 24 hours post-infection. Specimens from nasal washing have been taken up to 14 dpi to evaluate viral transmission and shedding. Every day, clinical symptoms were evaluated, while viral RNA in nasal washing samples and seroconversion were evaluated by RT-qPCR and hemagglutination inhibition assay, respectively. All animals (infection and transmission subgroup) remained clinically stable with no visible disease symptoms. All directly inoculated guinea pigs supported efficient replication of virus, with high viral RNA loads between 1 and 6 dpi. One contact animal had evidence of in-contact transmission, which showed progressive viral replication and seroconversion, while the remaining contact animals exhibited low-level or transient viral RNA detection without detectable antibody responses. This study reveals that the wild-type A/duck/India/11TR05/2021 H5N1 virus isolate belonging to clade 2.3.4.4b replicates efficiently in guinea pigs and has a limited transmission capacity to in-contact animals without prior mammalian adaptation. Continued molecular surveillance and experimental transmission studies are essential to detect early indicators of increased mammalian transmissibility and pandemic risk.