Why are diseases generally specific to a particular species

Question

"Zoonosis" is the process of transmitting a disease from an infected animal to a human. This suggests that animal-to-human transmission is not common. HIV is believed to have first spread to humans zoonotically, but has since mutated to a human-only strain.

This all raises the question: Why do diseases mostly just target a particular species? Aren't most metabolic processes very similar across species, especially within the same order and class? Dogs and cats can't catch the common cold, but they have similar diseases of their own.

There are obviously enough similarities that mice can be used in preliminary tests of human drugs, but the results are very tentative until human trials are done.

Answer 1

The pathogens which are responsible for certain diseases have adapted to their hosts. Viruses need to attach to structures on their cells they invade to replicate. These structures usually consist of proteins and are unique for the respective species (e.g. the ACE2 receptor in the case of Covid-19). During an infection, there will be billions of viruses released and some carry mutations, which are just mishaps in the replication process. In most cases, these errors are leading to a virus that is not viable or cannot infect, i.e. the mutated virus can't replicate and the mutation gets lost, but sometimes it can infect the host better and thus will have a higher chance to propagate. If this happens with a zoonotic pathogen after it has spread to a human, a new disease has emerged.