I define it by the fact that trans people are some of the most vulnerable groups in the entire world. (And I am saying this, fyi, as a cis person).

Because of the pervasive idea that genitals=sex (e.g. all women have vaginas, all men have penises), trans people do not get accepted as their actual gender. And that leads to violence, and death. In the USA, the average life span of a trans person is only 30-32 years old (compared to 78 years for the general population). The reasons for this decreased lifespan is myriad; the fact that trans individuals are far more routinely subject if violence/murder (78% of trans individuals report having been subject to assault), the higher rates of depression and suicide among trans people (50% of trans people attempt suicide at least once by the age of 20), and the high percentage of transgender homeless youth (it's hard to get hard statistics, but most estimates suggest that between 20-40% of homeless youth are transgender, compared to 5-10% of the overall population).

So, now obviously, this one comic doesn't do any of that. The point was more that it (accidentally) contributes to the idea that sex=genitals, which is the underlying cause of these deaths.