After sending out clients' newsletters, I'm often asked by them why someone would have unsubscribed. The worry seems to be that something in that particular issue made them disconnect. This is rarely the case.
I can't tell you all the reasons people unsubscribe but I can tell you that it is always about them. Lives change, interests change, jobs change, priorities change, time changes... all of these things can result in unsubscribes. You should never take unsubscribes personally.
You can typically expect list attrition - the natural pattern of unsubscribes you can consider normal - to be 25-30% per year. That industry-wide benchmark is not as useful as the one your own list will give you over time. You will see what your typical unsubscribe rate is. As long as you are growing your list faster than that rate, you shouldn't spend too much time worrying about unsubscribes.
On the other hand, if you are experiencing a sudden spike in unsubscribes, you will want to dig deeper into your recent email statistics and take a look at the content strategy in your last few newsletter issues. You should be able to pin down a problem - or a change that created a problem - and adjust. A strategy only works to the extent that you are willing to adjust based on feedback.
One thing that can cause a spike in unsubscribes is adding campaigns. For example, if you have been sending a monthly newsletter and then add a campaign for a large event, generating repeat sends, you might experience list exhaustion. Readers that are not interested in the event are feeling overwhelmed with messages about it.
A solution is to provide your readers with subscription options. Set up a second list for event emails so they can unsubscribe from those messages but still receive your newsletter. You will want to consider this strategy if you send a newsletter and promotional emails, as well. Over time, you will see that some of your readers only want event notices, some only want your newsletter, and others want both. They will sort that out for themselves if you give them options.
Readers will unsubscribe from content they are not interested in. Publish content that is useful, relevant and interesting to your target market. Send on a consistent and reliable schedule. Then keep your eye on the unsubscribes... but don't spend your time worrying about them.